Both age and biological sex affect transplantation outcomes. We have recently shown in a large volume clinical analysis utilizing the SRTR data that graft survival is inferior in young female kidney transplant recipients. In this multi-factorial analysis, older female recipients presented with a trend towards improved transplant outcomes compared to both young female recipients and male recipients of any age. Those data supported by reports of those of others suggest that sex and age impact alloimmune responses both, individually and synergistically. Biological sex and hormone levels change throughout a lifetime with recognized effects on longevity in addition to an impact on the development and course of several disease preconditions. Detailed mechanisms of those sex and age-specific aspects have thus far been studied outside of transplantation. Effects on alloimmunity are largely unknown. Moreover, the combinatorial impact that both, biological sex and age have on transplant outcomes is not understood. Here, we summarize available data that analyze how age in combination with biological sex may shape alloimmune responses and affect transplant outcomes.

Berberine, which is a traditional Chinese medicine can inhibit tumorigenesis by inducing tumor cell apoptosis. However, the immunoregulatory of effects berberine on T cells remains poorly understood. Here, we first examined whether berberine can prolong allograft survival by regulating the recruitment and function of T cells. Using a major histocompatibility complex complete mismatch mouse heterotopic cardiac transplantation model, we found that the administration of moderate doses (5 mg/kg) of berberine significantly prolonged heart allograft survival to 19 days and elicited no obvious berberine-related toxicity. Compared to that with normal saline treatment, berberine treatment decreased alloreactive T cells in recipient splenocytes and lymph node cells. It also inhibited the activation, proliferation, and function of alloreactive T cells. Most importantly, berberine treatment protected myocardial cells by decreasing CD4+ and CD8+ T cell infiltration and by inhibiting T cell function in allografts. In vivo and in vitro assays revealed that berberine treatment eliminated alloreactive T lymphocytes via the mitochondrial apoptosis pathway, which was validated by transcriptome sequencing. Taken together, we demonstrated that berberine prolongs allograft survival by inducing apoptosis of alloreactive T cells. Thus, our study provides more evidence supporting the potential use of berberine in translational medicine.

The impact on morbidity and mortality of Community Acquired Respiratory Virus (CARV) infections in patients undergoing Allogeneic Hematopoietic Cell Transplant (HCT) is widely studied. Here we give an overview of the current literature on the incidence and chance of progression to severe disease in this highly immune compromised population. We discuss the issue whether it is predominantly direct viral damage that causes clinical deterioration, or that it is in fact the allogeneic immuneresponse to the virus that is most important. This is an important question as it will guide therapeutic decision making. It asks for further collaborative studies focusing on sensitive surveillance with PCR techniques and relating clinical data with parameters of immune reconstitution.

UNASSIGNED: Allogeneic stem cell transplantation (allo-SCT) and donor lymphocyte infusions (DLI) may induce a graft-versus-tumor effect in pediatric sarcoma patients. Here, we describe general feasibility, toxicity and efficacy of DLI after allo-SCT.
UNASSIGNED: 4 of 8 patients responded. ES#4 had stable disease (SD) for 9 months after DLI and RMS#4 partial response for 8 months with combined hyperthermia/chemotherapy. In ES#4, DLI led to SD for 6 months and reverted residual disease before allo-SCT into complete remission. After DLI, ES#4 and RMS#4 developed acute GvHD (°III-°IV), ES#4 also developed chronic GvHD. 5 patients including ES#4 lived longer than expected. Median survival after allo-SCT was 2.3 years, post-relapse survival (PRS) was 13 months. Off note, HLA-mismatched DLI were associated with a trend towards increased survival after allo-SCT and increased PRS compared to HLA-matched DLI (23 versus 3 months).
UNASSIGNED: We studied eight adolescents and young adults (AYAs) with advanced Ewing sarcoma (ES#1-4) and rhabdomyosarcoma (RMS#1-4) who received DLI. Escalating doses ranged from 2.5 × 104 to 1 × 108 CD3+ cells/kg body weight. AYAs were evaluated for response to DLI, graft-versus-host disease (GvHD) and survival.
UNASSIGNED: DLI after allo-SCT may control advanced pediatric sarcoma in AYAs with controllable toxicity.